The principal function of a wound dressing is to provide an optimum healing environment. No one dressing is appropriate for all wounds and the choice of a wound dressing is dependent on the cause, presence of infection, wound type and size, stage of wound healing, cost, and patient acceptability (Findlay D., Aust. Fam Physician, 1994:23(5):824-839). According to Lawrence (Lawrence, J. C., Injury, 1982; 13:500-512), dressing material should be sterile, strong, absorbent, protective, inexpensive, and conform to the contours of the body. It should be nontoxic, hypoallergenic, and free of particulate material that may shed into the wound. Also, it should be easy to remove without it adhering to the wound and have an acceptable appearance to patients, nursing staff, and others.
Wound dressings can be classified as either primary or secondary. Primary dressings are placed directly over the wound. They provide protection, support, and absorption, prevent desiccation and infection, and serve as an adhesive base for the secondary dressing. Secondary dressings provide additional support, absorption, protection, compression, and occlusion. Often the secondary dressing serves as a pressure dressing.
There are a wide variety of dressings available to accomplish the essential goals of topical therapy, which are to provide adequate oxygen and circulation to the tissues, insulate and protect the healing wound, eliminate clinical infection by removing excess exudate, maintain a clean and moist environment, and obtain complete wound closure. Several different types of products may be needed as the wound progresses through the healing stages. These products include alginates, which form a gel covering over the wound, cleansers, which clean the wound site, collagen, a non-adherent covering that stimulates cellular migration, composites and enzymatic debriders, which facilitate autolytic debridement, exudate absorbers and foams, which fill the dead space in a wound, medicated gauze products, to treat and control infection, hydrocolloids and hydrogels, which reduce pain and facilitate autolytic debridement, pouches, to collect and contain drainage, skin sealants, and transparent films which reduce friction and facilitate autolytic debridement (Robert G. Smith, Wound Care Product Selection, U.S. Pharmacist, 4/2003). These products have attributes in treating various and different stages of wounds, however all have limitations. For example, alginates can possibly dehydrate the wound bed, give off foul odors and are contraindicated for use in the presence of dry eschar, on third degree burns and surgical implantation. Collagen dressings are also contraindicated for use in third degree burns and necrotic wounds. Gauze bandages, which are rendered non-adherent by incorporating petrolatum, still have a tendency to tear away new skin in removal and shed lint into the wound. In addition, they are non-absorbent. Hydrocolloids dressing are difficult to remove and malodorous yellow-brown drainage fluid typically collects under these dressings. Foams are not recommended for wounds with no exudates or wounds with dry eschar. Current hydrogel dressings have many advantages as compared to other products, but since they contain a large amount of water (80-90%), they are non-absorbent and not recommended for use on heavily exuding wounds, and if used alone, do not keep bacteria out of the wound.
This overview has been presented regarding wounds and different treatment modalities, and it is also important that a detailed description of polymer hydrogels be given since this invention pertains to hydrogel wound dressings and biomaterials.
A gel is a three-dimensional polymeric network that has absorbed a liquid to form a stable, usually soft and pliable, composition having a non-zero shear modulus. When the liquid absorbed by a gel is water, the gel is called a hydrogel. Water may comprise a significant weight percent of a hydrogel. This, plus the fact that many hydrogel-forming polymers are biologically inert, makes hydrogels particularly useful in a wide variety of biomedical applications.
For example, hydrogels are widely used in soft contact lens. They are also used as burn and wound dressings, with and without incorporated drugs that can be released from the gel matrix to aid in the healing process (e.g., see U.S. Pat. Nos. 3,063,685 and 4,272,518). Hydrogels have been used as coatings to improve the wettability of the surfaces of medical devices such as blood filters (U.S. Pat. No. 5,582,794). They have also found utility as devices for the sustained release of biologically active substances. For example, U.S. Pat. No. 5,292,515 discloses a method of preparing a hydrophilic reservoir drug delivery device. The '515 patent discloses that drug release rates can be controlled by changing the water content of the hydrogel subcutaneous implant, which directly affects its permeability coefficient.
In all the above applications, the gel or hydrogel is in bulk form, that is, it is an amorphous mass of material with no discernable regular internal structure. Bulk hydrogels have slow swelling rates due to the large internal volume relative to the surface area through which water must be absorbed. Furthermore, a substance dissolved or suspended in the absorbed water will diffuse out of the gel at a rate that depends on the distance it must travel to reach the surface of the gel. That is, molecules near the surface of the hydrogel will escape quickly, whereas molecules deeper within the matrix will take a much longer time to reach the outer surface of the gel. This situation can be ameliorated to some extent by using particulate gels. If each particle is sufficiently small, substances dispersed in the particles will diffuse to the surface and be released at approximately the same time.
Particulate gels can be formed by a number of procedures such as direct or inverse emulsion polymerization (Landfester, et al., Macromolecules, 2000, 33:2370) or they can be created from bulk gels by drying the gel and then grinding the resulting xerogel to particles of a desired size. The particles can then be re-solvated to form particulate gels. Particles having sizes in the micro (10−6 meters (m)) to nano (10−9 m) diameter range can be produced by this means. Molecules of a substance occluded by particles in these size ranges will all have about the same distance to travel to reach the outer surface of the particle and will exhibit near zero-order release kinetics. However, particulate gels have their problems. For instance, it is difficult to control the dissemination of the particles to, and localization at, a selected target site. Furthermore, while bulk hydrogels can be rendered shape-retentive, making them useful as biomaterials in a variety of medical applications, currently available particulate gels, cannot.
U.S. Pat. No. 7,351,430 B2 discloses a shape-retentive aggregate formed from hydrogel particles, thus combining the shape-retentiveness of bulk hydrogels with the substance release control of particulate gels. The '430 patent discloses a method of forming the shape-retentive aggregates comprising preparing a suspension of hydrogel particles in water or other polar liquid and concentrating the suspension until the particles coalesce into a shape-retentive aggregate held together by non-covalent bond physical forces including but not limited to hydrophobic/hydrophilic interactions and hydrogen bonds. The devices of this invention are particularly useful, for example, as drug delivery implants, tissue scaffolds for cartilage or bone repair, and moldable drug eluting contact lenses and catheters.
Co-pending U.S. Patent Application Publication No. US 2005/0118270A1 discloses a method of forming shape-retentive aggregates in situ, such that the shape of the aggregate would be dictated by the shape of the locus of application. Aggregate formation is accomplished by introducing a suspension of gel particles dispersed in a polar liquid, preferably water, wherein the gel particles have an absolute zeta potential enabling the particles to remain dispersed, into a receiving medium wherein the absolute zeta potential of the gel particles is reduced. The gel particles coalesce into a shape-retentive aggregate held together by non-covalent bond physical forces comprising hydrophobic-hydrophilic interactions and hydrogen bonding. Applications include, but not limited to biomedical uses such as joint reconstruction, wound repair, drug deliver implants formed in situ and cosmetic and reconstructive surgery.